The purpose of this proposed study is to characterize genes related to both risk of sarcopenia and muscle adaptation to strength training. Although strength training may reverse some of the muscle losses associated with sarcopenia, substantial inter-individual variability has been reported in both sarcopenia and muscle adaptation to strength training. These observations combined with the substantial heritability of muscle mass noted in twin studies (up to 80%) suggest a role for genetic factors in both muscle loss and adaptation. We hypothesize that differences in muscle-specific gene expression will party explain age- and sex related differences in muscle mass and strength, as well as muscle adaptation to strength training. Also, we hypothesize that polymorphisms within these genes will play a role in determining risk for sarcopenia. To test these hypotheses, the applicant will first (Study 1) assess "global" muscle-specific gene expression in young and older subjects before and after strength training using the SAGE (serial analysis of gene expression) technique. SAGE will allow the complete cataloging of changes in muscle-specific mRNA levels in response to strength training in these men and women, thus identifying potential "candidate" genes the may be involved in muscle loss and adaptation. In Study 2, the "candidate" genes identified in Study 1 will be assessed in muscle samples from 40 young and older men and women who have been previously strength trained at UMD, thus allowing the study of genes important in determining age- and sex-related differences in muscle mass, strength, and adaptation. In Studies 3 &4, the "candidate" genes identified from Studies 1 &2 will be assessed for polymorphisms and studied in both a large cross-sectional cohort of subjects (~700; 19-94yr.), as well as ~70 subjects who have been previously strength trained at UMD.